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1.
Future Oncol ; : 1-9, 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38861296

RESUMEN

Aim: There is little consensus on salvage management of glioblastoma after recurrence, for lack of evidence. Materials & methods: A retrospective study of treatments in patients with recurrent glioblastoma. Results: Surgery at recurrence was related to better overall survival (OS) and progression-free survival (PFS). Surgery at recurrence, Karnofsky index, MGMT methylation status, younger age at diagnosis and number of chemotherapy cycles were positive factors for OS and PFS. The benefit of OS was relevant for a second surgery performed at least 9 months after the first one. Systemic treatments after the second surgery were linked to an improved PFS. Conclusion: Younger age, Karnofsky index, MGMT methylation status and a median time between surgeries ≥9 months may be criteria for eligibility for surgery at recurrence.


[Box: see text].

2.
J Transl Med ; 21(1): 215, 2023 03 23.
Artículo en Inglés | MEDLINE | ID: mdl-36959606

RESUMEN

BACKGROUND: This study aimed to characterize the genetic profile of patients with glioma and discuss the impact of next-generation sequencing in glioma diagnosis and treatment. METHODS: Between 2019 and 2022, we analyzed the genetic profile of 99 patients with glioma through the Oncomine Focus Assay. The assay enables the detection of mutations in 52 driver genes, including single nucleotide variants (SNVs), copy number variants (CNVs), and gene fusions. We also collected and analyzed patients' clinic characteristics and treatment outcomes. RESULTS: Over a period of 35 months, 700 patients with glioma followed by our neuro-oncology unit were screened, and 99 were enrolled in the study; most of the patients were excluded for inadequate non-morphological MRI or lack/inadequacy of the tissue samples. Based on our findings, most patients with glioma present mutations, such as SNVs, CNVs or gene fusions. Our data were similar to those reported by The Cancer Genome Atlas Program in terms of frequency of SNVs and CNVs, while we observed more cases of gene fusions. Median overall survival, progression-free survival, and time to progression were significantly lower for patients with grade VI glioblastoma than those with other gliomas. Only four patients were offered a targeted treatment based on the mutation detected; however, only one received treatment, the others could not receive the selected treatment because of worsening clinical status. CONCLUSION: Routine timely molecular profiling in patients with glioma should be implemented to offer patients an individualized diagnostic approach and provide them with advanced targeted therapy options if available.


Asunto(s)
Neoplasias Encefálicas , Glioblastoma , Glioma , Humanos , Glioma/diagnóstico , Glioma/genética , Glioma/terapia , Mutación/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Variaciones en el Número de Copia de ADN/genética , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/terapia
3.
J Transl Med ; 21(1): 725, 2023 10 16.
Artículo en Inglés | MEDLINE | ID: mdl-37845764

RESUMEN

BACKGROUND: Molecular Tumor Boards (MTB) operating in real-world have generated limited consensus on good practices for accrual, actionable alteration mapping, and outcome metrics. These topics are addressed herein in 124 MTB patients, all real-world accrued at progression, and lacking approved therapy options. METHODS: Actionable genomic alterations identified by tumor DNA (tDNA) and circulating tumor DNA (ctDNA) profiling were mapped by customized OncoKB criteria to reflect diagnostic/therapeutic indications as approved in Europe. Alterations were considered non-SoC when mapped at either OncoKB level 3, regardless of tDNA/ctDNA origin, or at OncoKB levels 1/2, provided they were undetectable in matched tDNA, and had not been exploited in previous therapy lines. RESULTS: Altogether, actionable alterations were detected in 54/124 (43.5%) MTB patients, but only in 39 cases (31%) were these alterations (25 from tDNA, 14 from ctDNA) actionable/unexploited, e.g. they had not resulted in the assignment of pre-MTB treatments. Interestingly, actionable and actionable/unexploited alterations both decreased (37.5% and 22.7% respectively) in a subset of 88 MTB patients profiled by tDNA-only, but increased considerably (77.7% and 66.7%) in 18 distinct patients undergoing combined tDNA/ctDNA testing, approaching the potential treatment opportunities (76.9%) in 147 treatment-naïve patients undergoing routine tDNA profiling for the first time. Non-SoC therapy was MTB-recommended to all 39 patients with actionable/unexploited alterations, but only 22 (56%) accessed the applicable drug, mainly due to clinical deterioration, lengthy drug-gathering procedures, and geographical distance from recruiting clinical trials. Partial response and stable disease were recorded in 8 and 7 of 19 evaluable patients, respectively. The time to progression (TTP) ratio (MTB-recommended treatment vs last pre-MTB treatment) exceeded the conventional Von Hoff 1.3 cut-off in 9/19 cases, high absolute TTP and Von Hoff values coinciding in 3 cases. Retrospectively, 8 patients receiving post-MTB treatment(s) as per physician's choice were noted to have a much longer overall survival from MTB accrual than 11 patients who had received no further treatment (35.09 vs 6.67 months, p = 0.006). CONCLUSIONS: MTB-recommended/non-SoC treatments are effective, including those assigned by ctDNA-only alterations. However, real-world MTBs may inadvertently recruit patients electively susceptible to diverse and/or multiple treatments.


Asunto(s)
Neoplasias , Estados Unidos , Humanos , National Cancer Institute (U.S.) , Estudios Retrospectivos , Mutación , Neoplasias/genética , ADN de Neoplasias/genética , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Biomarcadores de Tumor/genética
4.
Neurol Sci ; 44(8): 2897-2902, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-36882595

RESUMEN

BACKGROUND: End-of-life in patients with brain cancer presents special challenges, and palliative care approach is underutilized. Patients with brain cancer, in the last months of life, receive frequent hospital readmissions, highlighting bad end-of-life care quality. Early integration of palliative care improves quality of care in advanced stage of disease and patient's quality of death. PURPOSE: We retrospectively analyzed a consecutive series of patients with brain cancer discharged after diagnosis to evaluate pattern of treatment and rate of hospital readmission in the last months of life. DESIGN: Data were collected from the Lazio Region Healthcare database. SETTING: Adult patients discharged with diagnosis ICD-9 191.* between January 1, 2010, and December 31, 2019 were included. RESULTS: A total of 6672 patients were identified, and 3045 deaths were included. In the last 30 days 33% were readmitted to the hospital and 24.2% to the emergency room. 11.7% were treated with chemotherapy and 6% with radiotherapy. Most indicators of end-of-life care showed wide variability by hospital of discharge. CONCLUSIONS: Strategies to improve quality of care at the end of life and to decrease re-hospitalization and futile treatments are becoming increasingly important to improve quality of death and reduce healthcare costs. Variability observed by hospital of discharge indicates the lack of a standard approach to end-of-life care.


Asunto(s)
Neoplasias Encefálicas , Neoplasias , Cuidado Terminal , Adulto , Humanos , Estudios Retrospectivos , Hospitalización , Cuidados Paliativos , Neoplasias Encefálicas/terapia
5.
Neurol Sci ; 44(3): 1073-1075, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36567410

RESUMEN

BACKGROUND: WHO grade II and III meningiomas are more invasive than grade I malignancies and determine patients' shorter overall survival. Their tendency to recur after treatment has represented an important therapeutic challenge because of the limited treatment strategies at recurrence. Angiogenesis and mechanistic target of rapamycin (mTOR) activation are two of the main features of higher grade meningiomas, determining invasiveness and tendency to relapse. While these options prove promising, available clinical data on mTOR inhibitors' efficacy are somewhat limited. CASE STUDY: We report a case of a 25-year-old female patient diagnosed with a right parasagittal occipital anaplastic meningioma (grade III WHO) in 2013. The patient underwent multiple treatments and, in 2019, a further recurrence occurred. The patient reported an mTOR mutation, and it is for this reason that the MTB approved treatment with everolimus and bevacizumab. Therapy was administered in May 2019, and partial response and prolonged disease control was obtained in November 2021, when progression took place. The patient's death occurred in March 2022. CONCLUSIONS: This case report provides evidence on the efficacy of mTOR inhibitors as a treatment option in recurrent meningiomas. Furthermore, it highlights the importance of performing a molecular analysis as a preliminary step towards targeting the mTOR pathway.


Asunto(s)
Neoplasias Meníngeas , Meningioma , Femenino , Humanos , Adulto , Meningioma/tratamiento farmacológico , Meningioma/genética , Meningioma/patología , Neoplasias Meníngeas/tratamiento farmacológico , Neoplasias Meníngeas/genética , Neoplasias Meníngeas/patología , Medicina de Precisión , Inhibidores mTOR , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/patología , Serina-Treonina Quinasas TOR/genética , Serina-Treonina Quinasas TOR/uso terapéutico
6.
Neurol Sci ; 44(5): 1749-1754, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36598619

RESUMEN

BACKGROUND: In 2017, the European Association of Neuro-Oncology (EANO) published the guideline for palliative care in adults with glioma. The Italian Society of Neurology (SIN), the Italian Society for Palliative Care (SICP), and the Italian Association for Neuro-Oncology (AINO) joined forces to update the guideline, and adapt it to the Italian context. AIM: We involved patients, caregivers, and (herein presented) healthcare professionals (HPs) in the formulation of the guideline clinical questions. DESIGN AND PARTICIPANTS: Online survey of Italian HPs experienced in the care of patients with glioma. Participants rated the importance of 14 pre-specified intervention topics on a 0/10 scale and gave their free comments. RESULTS: Of 244 participants, 149 (61%) were palliative medicine (PM) HPs and 95 Neuro HPs. Their mean age was 48.9 years, 63% were women, and 48% had over 12 years of experience in the care of glioma patients. Physicians were 68%, followed by nurses (28%), psychologists (7%), therapists (3%), and social workers (2%). Most HPs rated the pre-specified topics as important (score ≥ 7) or critical (score ≥ 9), with some differences between PM and Neuro HP groups. There were 58 free comments: 46 (78%) on nine pre-specified topics, and 13 on four new topics, three of which were guideline-pertinent ("caregiver's support and education"; "family physician's training in neuro-oncology"; and "PM HPs' training in neuro-oncology"). CONCLUSIONS: Participation in the survey was high and information-rich, between-group rating differences reflecting HP background. Participants endorsed the 14 intervention topics devised by the guideline panel and identified three additional topics.


Asunto(s)
Glioma , Cuidados Paliativos , Humanos , Adulto , Femenino , Persona de Mediana Edad , Masculino , Glioma/terapia , Personal de Salud , Italia , Cuidadores
7.
Neurol Sci ; 44(7): 2491-2499, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-36809422

RESUMEN

BACKGROUND: In 2017, the European Association for Neuro-Oncology (EANO) published the guideline for palliative care (PC) in adults with glioma. The Italian Society of Neurology (SIN), the Italian Association for Neuro-Oncology (AINO), and the Italian Society for Palliative Care (SICP) joined forces to update and adapt this guideline to the Italian context and aimed to involve patients and carers in the formulation of the clinical questions. METHODS: During semi-structured interviews with glioma patients and focus group meetings (FGMs) with family carers of deceased patients, participants rated the importance of a set of pre-specified intervention topics, shared their experience, and suggested additional topics. Interviews and FGMs were audio-recorded, transcribed, coded, and analyzed (framework and content analysis). RESULTS: We held 20 interviews and five FGMs (28 carers). Both parties considered the pre-specified topics as important, chiefly information/communication, psychological support, symptoms management, and rehabilitation. Patients aired the impact of focal neurological and cognitive deficits. Carers reported difficulties in dealing with patient's behavior and personality changes and appreciated the preservation of patient's functioning via rehabilitation. Both affirmed the importance of a dedicated healthcare path and patient's involvement in the decision-making process. Carers expressed the need to be educated and supported in their caregiving role. CONCLUSIONS: Interviews and FGMs were well informative and emotionally challenging. Both parties confirmed the importance of the pre-specified topics, and carers suggested one additional topic: education/support to caregivers. Our findings strengthen the importance of a comprehensive care approach and of addressing the needs of both patients and their family carers.


Asunto(s)
Glioma , Cuidados Paliativos , Humanos , Adulto , Cuidadores/psicología , Grupos Focales , Atención a la Salud , Glioma/terapia
8.
Int J Mol Sci ; 24(9)2023 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-37175436

RESUMEN

The inclusion of fluorine atoms or heterocyclic moiety into drug structures represents a recurrent motif in medicinal chemistry. The combination of these two features is constantly appearing in new molecular entities with various biological activities. This is demonstrated by the increasing number of newly synthesized fluorinated heterocyclic compounds among the Food and Drug Administration FDA-approved drugs. In this review, the biological activity, as well as the synthetic aspects, of 33 recently FDA-approved fluorinated heterocyclic drugs from 2016 to 2022 are highlighted.


Asunto(s)
Compuestos Heterocíclicos , Preparaciones Farmacéuticas , Compuestos Heterocíclicos/farmacología , Compuestos Heterocíclicos/química , Flúor/química , Química Farmacéutica
9.
Int J Mol Sci ; 24(11)2023 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-37298560

RESUMEN

Cystic Fibrosis (CF) is an autosomal recessive genetic disease caused by mutations in the CFTR gene, coding for the CFTR chloride channel. About 10% of the CFTR gene mutations are "stop" mutations that generate a premature termination codon (PTC), thus synthesizing a truncated CFTR protein. A way to bypass PTC relies on ribosome readthrough, which is the ribosome's capacity to skip a PTC, thus generating a full-length protein. "TRIDs" are molecules exerting ribosome readthrough; for some, the mechanism of action is still under debate. We investigate a possible mechanism of action (MOA) by which our recently synthesized TRIDs, namely NV848, NV914, and NV930, could exert their readthrough activity by in silico analysis and in vitro studies. Our results suggest a likely inhibition of FTSJ1, a tryptophan tRNA-specific 2'-O-methyltransferase.


Asunto(s)
Regulador de Conductancia de Transmembrana de Fibrosis Quística , Fibrosis Quística , Humanos , Codón sin Sentido/genética , Fibrosis Quística/genética , Fibrosis Quística/metabolismo , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Regulador de Conductancia de Transmembrana de Fibrosis Quística/metabolismo , Metiltransferasas/metabolismo , Proteínas Nucleares/genética , ARN de Transferencia/genética , Triptófano/genética
10.
Int J Mol Sci ; 24(20)2023 Oct 11.
Artículo en Inglés | MEDLINE | ID: mdl-37894764

RESUMEN

Nonsense mutations cause several genetic diseases such as cystic fibrosis, Duchenne muscular dystrophy, ß-thalassemia, and Shwachman-Diamond syndrome. These mutations induce the formation of a premature termination codon (PTC) inside the mRNA sequence, resulting in the synthesis of truncated polypeptides. Nonsense suppression therapy mediated by translational readthrough-inducing drugs (TRIDs) is a promising approach to correct these genetic defects. TRIDs generate a ribosome miscoding of the PTC named "translational readthrough" and restore the synthesis of full-length and potentially functional proteins. The new oxadiazole-core TRIDs NV848, NV914, and NV930 (NV) showed translational readthrough activity in nonsense-related in vitro systems. In this work, the possible off-target effect of NV molecules on natural termination codons (NTCs) was investigated. Two different in vitro approaches were used to assess if the NV molecule treatment induces NTC readthrough: (1) a study of the translational-induced p53 molecular weight and functionality; (2) the evaluation of two housekeeping proteins' (Cys-C and ß2M) molecular weights. Our results showed that the treatment with NV848, NV914, or NV930 did not induce any translation alterations in both experimental systems. The data suggested that NV molecules have a specific action for the PTCs and an undetectable effect on the NTCs.


Asunto(s)
Genes Esenciales , Proteína p53 Supresora de Tumor , Codón de Terminación , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Biosíntesis de Proteínas , Codón sin Sentido
11.
Medicina (Kaunas) ; 59(7)2023 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-37512031

RESUMEN

Background: Femoral neck fractures are an epidemiologically significant issue with major effects on patients and health care systems, as they account for a large percentage of bone injuries in the elderly. Hip hemiarthroplasty is a common surgical procedure in the treatment of displaced femoral neck fractures. Several surgical approaches may be used to access the hip joint in case of femoral neck fractures, each with its own benefits and potential drawbacks, but none of them has consistently been found to be superior to the others. This article aims to systematically review and compare the different approaches in terms of the complication rate at the last follow-up. Methods: an in-depth search on PubMed/Scopus/Web of Science databases and a cross-referencing search was carried out concerning the articles comparing different approaches in hemiarthroplasty and reporting detailed data. Results: A total of 97,576 hips were included: 1030 treated with a direct anterior approach, 4131 with an anterolateral approach, 59,110 with a direct lateral approach, and 33,007 with a posterolateral approach. Comparing the different approaches, significant differences were found in both the overall complication rate and the rate of revision surgery performed (p < 0.05). In particular, the posterolateral approach showed a significantly higher complication rate than the lateral approach (8.4% vs. 3.2%, p < 0.001). Furthermore, the dislocation rate in the posterolateral group was significantly higher than in the other three groups considered (p < 0.026). However, the posterolateral group showed less blood loss than the anterolateral group (p < 0.001), a lower intraoperative fractures rate than the direct anterior group (p < 0.035), and shorter mean operative time than the direct lateral group (p < 0.018). Conclusions: The posterolateral approach showed a higher complication rate than direct lateral approach and a higher prosthetic dislocation rate than the other three types of surgical approaches. On the other hand, patients treated with posterolateral approach showed better outcomes in other parameters considered, such as mean operative time, mean blood loss and intraoperative fractures rate. The knowledge of the limitations of each approach and the most common associated complications can lead to choosing a surgical technique based on the patient's individual risk.


Asunto(s)
Artroplastia de Reemplazo de Cadera , Fracturas del Cuello Femoral , Hemiartroplastia , Humanos , Anciano , Artroplastia de Reemplazo de Cadera/efectos adversos , Hemiartroplastia/efectos adversos , Hemiartroplastia/métodos , Fracturas del Cuello Femoral/cirugía , Articulación de la Cadera , Cadera , Resultado del Tratamiento
12.
Future Oncol ; 18(15): 1839-1848, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35196869

RESUMEN

Aim: We performed longitudinal evaluations of the neurocognitive status in glioma patients to describe possible variations over the course of illness. Materials and methods: Glioma patients underwent a complete battery of standardized neuropsychological tests pre-radiotherapy at 6, 12 and 24 months. Results: We enrolled 130 patients, 67.7% of whom had a deficit in at least one cognitive domain. The most affected domains included executive function (n = 68, 52.3%), long-term memory (n = 46, 35.3%) and short-term memory (n = 39, 30%). At follow-up, cognitive status worsened in 31.5%, remained unchanged in 38.4% and improved in 30.1% of patients. Conclusion: This is one of few studies investigating longitudinal neurocognitive status in a wide sample of patients to monitor neuropsychological changes due to tumor progression and treatment administration.


Malignant gliomas are brain tumors with dismal prognosis that can affect patients' neurocognitive status. We performed longitudinal neuropsychological assessments to describe variations due to illness progression and treatment administration. Patients underwent a battery of standardized neuropsychological tests tapping into different cognitive domains (memory, attention, abstract reasoning, executive functions, learning), pre-radiotherapy and at 6, 12 and 24 month follow-up. We enrolled 130 patients, and almost 70% of them had at least one cognitive deficit. The most affected domains were executive function and long- and short-term memory. At follow-up assessments, cognitive status worsened in one-third of patients, whereas it remained unchanged or improved in two-thirds of patients. This is one of few longitudinal studies investigating cognitive function in a large sample of patients to monitor changes along the illness course.


Asunto(s)
Neoplasias Encefálicas , Glioma , Neoplasias Encefálicas/complicaciones , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/terapia , Cognición , Glioma/complicaciones , Glioma/patología , Glioma/terapia , Humanos , Pruebas Neuropsicológicas
13.
Neurol Sci ; 43(9): 5533-5541, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35641731

RESUMEN

BACKGROUND: The majority of patients with glioblastoma (GBM) experience disease progression. At recurrence, treatment options have limited efficacy. Many studies report a limited and short duration response rate. Although clinical trials represent the "gold standard" for providing evidence on efficacy of specific treatment strategies, real-world data can be considered more representative of the "real" GBM population. OBJECTIVE: To describe the management of GBM recurrence in a large real-world sample. METHODS: We analysed retrospectively the data stored in the database of the Neuro-oncology Unit, IRCCS "Regina Elena" National Cancer Institute, Rome, Italy. We considered only data of patients with histological diagnosis of GBM and disease recurrence during their follow-up. We excluded patients who did not receive treatment after the diagnosis. RESULTS: We analysed 422 patients (64% males, 36% females) with a mean age of 59.6 (range 16-87) years. At GBM recurrence, 135 (32.0%) patients underwent palliative care, and 287 (68.0%) underwent other treatments. Patients on palliative care were older, had a worse performance status, and a shorter time between GBM diagnosis and its recurrence. Patients who received chemotherapy in combination with other treatments (surgery and/or radiation therapy) at GBM recurrence had a longer survival than those in palliative care (p < 0.001). Surgery or radiation therapy alone did not have any effect on survival as compared with palliative care (p < 0.001). CONCLUSION: This study confirms the importance of a multidisciplinary approach even at GBM recurrence, suggesting that combination treatments play a key role in management of disease.


Asunto(s)
Neoplasias Encefálicas , Glioblastoma , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/terapia , Terapia Combinada , Femenino , Glioblastoma/patología , Humanos , Masculino , Persona de Mediana Edad , National Cancer Institute (U.S.) , Recurrencia Local de Neoplasia/radioterapia , Estudios Retrospectivos , Estados Unidos , Adulto Joven
14.
Neurol Sci ; 43(6): 3519-3522, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35397014

RESUMEN

BACKGROUND: The BNT162b2 vaccine conferred 95% protection against COVID-19 in people aged 16 years or older. OBJECTIVE: The aim of this observational study was to evaluate safety and efficacy of vaccine in patients affected by primary brain tumor (PBT). METHODS: We proposed COVID-19 vaccine to all patients affected by PBT followed by Neuroncology Unit of National Cancer Institute Regina Elena. RESULTS: 102 patients received the first dose, 100 the second, and 73 patients received the booster dose. After first dose, we observed one patient with fever and severe fatigue, while after the second one, we recorded adverse events in ten patients. No correlation was observed between adverse events and comorbidities. CONCLUSIONS: The COVID-19 vaccine is safe and well tolerated in PBT patients.


Asunto(s)
Neoplasias Encefálicas , COVID-19 , Vacuna BNT162 , Neoplasias Encefálicas/complicaciones , COVID-19/prevención & control , Vacunas contra la COVID-19/efectos adversos , Humanos , ARN Mensajero , SARS-CoV-2
15.
J Biol Chem ; 295(44): 14807-14825, 2020 10 30.
Artículo en Inglés | MEDLINE | ID: mdl-32737202

RESUMEN

The pathological aggregation of tau plays an important role in Alzheimer's disease and many other related neurodegenerative diseases, collectively referred to as tauopathies. Recent evidence has demonstrated that tau oligomers, small and soluble prefibrillar aggregates, are highly toxic due to their strong ability to seed tau misfolding and propagate the pathology seen across different neurodegenerative diseases. We previously showed that novel curcumin derivatives affect preformed tau oligomer aggregation pathways by promoting the formation of more aggregated and nontoxic tau aggregates. To further investigate their therapeutic potential, we have extended our studies o disease-relevant brain-derived tau oligomers (BDTOs). Herein, using well-characterized BDTOs, isolated from brain tissues of different tauopathies, including Alzheimer's disease, progressive supranuclear palsy, and dementia with Lewy bodies, we found that curcumin derivatives modulate the aggregation state of BDTOs by reshaping them and rescue neurons from BDTO-associated toxicity. Interestingly, compound CL3 showed an effect on the aggregation pattern of BDTOs from different tauopathies, resulting in the formation of less neurotoxic larger tau aggregates with decreased hydrophobicity and seeding propensity. Our results lay the groundwork for potential investigations of the efficacy and beneficial effects of CL3 and other promising compounds for the treatment of tauopathies. Furthermore, CL3 may aid in the development of tau imaging agent for the detection of tau oligomeric strains and differential diagnosis of the tauopathies, thus enabling earlier interventions.


Asunto(s)
Biopolímeros/química , Bibliotecas de Moléculas Pequeñas/farmacología , Tauopatías/tratamiento farmacológico , Proteínas tau/metabolismo , Biopolímeros/metabolismo , Encéfalo/citología , Encéfalo/metabolismo , Células Cultivadas , Curcumina/análogos & derivados , Curcumina/farmacología , Diagnóstico Diferencial , Humanos , Neuronas/metabolismo , Bibliotecas de Moléculas Pequeñas/uso terapéutico , Tauopatías/diagnóstico , Proteínas tau/efectos de los fármacos
16.
BMC Cancer ; 21(1): 311, 2021 Mar 24.
Artículo en Inglés | MEDLINE | ID: mdl-33761916

RESUMEN

BACKGROUND: Breast cancer (BC) presents important physical and psychological challenges that should be appropriately addressed through continuous, integrated and individualized rehabilitation programs after treatment. In this study, we aimed to collect more information on the rehabilitation patterns and utilization of healthcare services by women with BC. METHODS: We retrospectively analyzed data from two archives of the Lazio Regional Health System Database to assess rehabilitation patterns in women diagnosed with BC in the Lazio region (Italy) in 2008. RESULTS: A total of 5538 women diagnosed with BC were considered in the present study. Most patients (81.7%) received outpatient rehabilitative care, consisting mainly of pathology-related interventions and, more rarely, disability-related interventions (mainly motor rehabilitation and rarely cognitive or psychological therapy). Few patients followed an inpatient (1.3%) or an intensive outpatient rehabilitation program (1.0%). CONCLUSION: Most patients do not receive adequate rehabilitation care during the first year after diagnosis. More information and better rehabilitation services should be provided to help patients with BC access rehabilitation programs. The study also suggests the importance of psychosocial and cognitive interventions, which is a major unmet need in women with BC.


Asunto(s)
Neoplasias de la Mama/rehabilitación , Vías Clínicas/estadística & datos numéricos , Aceptación de la Atención de Salud/estadística & datos numéricos , Pautas de la Práctica en Medicina/estadística & datos numéricos , Anciano , Atención Ambulatoria/estadística & datos numéricos , Femenino , Hospitalización/estadística & datos numéricos , Humanos , Italia , Persona de Mediana Edad , Calidad de Vida , Estudios Retrospectivos
17.
Future Oncol ; 17(26): 3445-3456, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34044585

RESUMEN

Background: Eribulin shows some activity in controlling brain metastasis in breast cancer. Methods: This observational, multicenter study evaluated brain disease control rates, survival and safety in patients with brain metastatic breast cancer treated with eribulin in clinical practice. Results: A total of 34 patients were enrolled (mean age 49 years, 91% with visceral metastases) and 29 were evaluable for brain disease. Fourteen achieved disease control and showed a longer time without progression: 10 months (95% CI: 2.3-17.7) versus 4 months (95% CI: 3.3-4.7) in the control group (p = 0.029). Patients with clinical benefits at 6 months had longer survival. Leukopenia and neutropenia were the most frequent grade 3-4 toxicities. Conclusion: Eribulin confirms its effectiveness in patients with brain metastatic breast cancer. Further studies on larger cohorts are needed to confirm the results.


Asunto(s)
Neoplasias Encefálicas/mortalidad , Neoplasias de la Mama/mortalidad , Furanos/uso terapéutico , Cetonas/uso terapéutico , Adulto , Anciano , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/secundario , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Tasa de Supervivencia
18.
Neurol Sci ; 42(5): 1879-1886, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-32954462

RESUMEN

BACKGROUND AND PURPOSE: Adult brainstem gliomas are rare primary brain tumours with heterogeneous clinical course. The low frequency of these tumours makes it difficult to achieve high-quality evidence regarding prognostic factors, adequate therapeutic approach and outcome in such patients. METHODS: In this retrospective study, we analysed clinical, radiological, molecular, prognostic and therapeutic factors in a series of 47 histologically proven adult brainstem gliomas recruited over a 20-year period (1998-2018). RESULTS: Twenty-two patients were male, 25 female with median age of 39 years. The tumour involved one brainstem segment in 20 cases and 2 or more segments in 27. Contrast enhancement was reported in 28 cases. Surgical procedures included biopsy in 26 cases and partial/total resection in the remaining 21. Histological diagnosis was of low-grade glioma in 23 patients, high-grade glioma in 22 and non-diagnostic in 2 cases. Data regarding molecular biology were available for 22 patients. Median overall survival was 35 months, in particular 16 months in high-grade glioma and 84 months in low-grade glioma. At univariate analysis, tumour grade was the only factor with a statistically significant impact on survival time (p = 0,003), whereas younger age, better performance status and total/subtotal resection showed a trend to more prolonged survival. This study also confirms safety of biopsy/surgery in adult brainstem glioma patients and shows a clear trend to a more frequent assessment of molecular biology data. CONCLUSIONS: Further prospective multicentre efforts, and hopefully clinical trials, are necessary to improve outcome in this neglected glioma patient population.


Asunto(s)
Neoplasias Encefálicas , Neoplasias del Tronco Encefálico , Glioma , Adulto , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/terapia , Neoplasias del Tronco Encefálico/diagnóstico por imagen , Neoplasias del Tronco Encefálico/genética , Neoplasias del Tronco Encefálico/terapia , Femenino , Glioma/diagnóstico por imagen , Glioma/genética , Glioma/terapia , Humanos , Italia/epidemiología , Masculino , Pronóstico , Estudios Retrospectivos
19.
Sensors (Basel) ; 21(16)2021 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-34450874

RESUMEN

In recent years, there has been a continuously growing interest in antioxidants by both customers and food industry. The beneficial health effects of antioxidants led to their widespread use in fortified functional foods, as dietary supplements and as preservatives. A variety of analytical methods are available to evaluate the total antioxidant capacity (TAC) of food extracts and beverages. However, most of them are expensive, time-consuming, and require laboratory instrumentation. Therefore, simple, cheap, and fast portable sensors for point-of-need measurement of antioxidants in food samples are needed. Here, we describe a smartphone-based chemosensor for on-site assessment of TAC of aqueous matrices, relying on the antioxidant-induced formation of gold nanoparticles. The reaction takes place in ready-to-use analytical cartridges containing an hydrogel reaction medium preloaded with Au(III) and is monitored by using the smartphone's CMOS camera. An analytical device including an LED-based lighting system was developed to ensure uniform and reproducible illumination of the analytical cartridge. The chemosensor permitted rapid TAC measurements of aqueous samples, including teas, herbal infusions, beverages, and extra virgin olive oil extracts, providing results that correlated with those of the reference methods for TAC assessment, e.g., oxygen radical absorbance capacity (ORAC).


Asunto(s)
Antioxidantes , Nanopartículas del Metal , Suplementos Dietéticos , Oro , Fenoles/análisis , Polifenoles , Teléfono Inteligente
20.
Int J Mol Sci ; 22(12)2021 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-34207956

RESUMEN

This review is a survey of recent advances in studies concerning the impact of poly- and perfluorinated organic compounds in aquatic organisms. After a brief introduction on poly- and perfluorinated compounds (PFCs) features, an overview of recent monitoring studies is reported illustrating ranges of recorded concentrations in water, sediments, and species. Besides presenting general concepts defining bioaccumulative potential and its indicators, the biodistribution of PFCs is described taking in consideration different tissues/organs of the investigated species as well as differences between studies in the wild or under controlled laboratory conditions. The potential use of species as bioindicators for biomonitoring studies are discussed and data are summarized in a table reporting the number of monitored PFCs and their total concentration as a function of investigated species. Moreover, biomolecular effects on taxonomically different species are illustrated. In the final paragraph, main findings have been summarized and possible solutions to environmental threats posed by PFCs in the aquatic environment are discussed.


Asunto(s)
Organismos Acuáticos/metabolismo , Bioacumulación , Monitoreo Biológico , Fluorocarburos/metabolismo , Semivida , Distribución Tisular
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